Implications of the antiviral drug favipiravir on rabies immunoglobulin for post-exposure prophylaxis of rabies in mice model with category III-like exposures
Implications of the antiviral drug favipiravir on rabies immunoglobulin for post-exposure prophylaxis of rabies in mice model with category III-like exposures
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DOI：
10.1016/j.antiviral.2022.105489
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发表时间：
2022-12-13
影响因子：
7.6
通讯作者：
Nishizono, Akira
中科院分区：
文献类型：
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作者：
Kimitsuki, Kazunori;Khan, Sakirul;Nishizono, Akira
狂犬病是由狂犬病病毒（RABV）引起的致命的人畜共患疾病，如果不及时应用由狂犬病免疫球蛋白（RIG）和狂犬病疫苗组成的适当的暴露后预防（PEP），死亡率几乎为100%。然而，这一点受到了RIG供应有限的挑战，特别是在资源有限的国家。在这项研究中，我们评估了抗病毒药物法匹拉韦作为RIG替代品治疗狂犬病感染小鼠的范围。在PEP方案中，用法匹拉韦代替RIG处理的RABV攻击小鼠中诱导了III类伤口。在100%的小鼠中，使用法匹拉韦后接种狂犬病疫苗可完全预防狂犬病相关死亡，即使在感染期间RABV传播至中枢神经系统后也是如此。此外，法匹拉韦和疫苗组的病毒中和抗体滴度显著高于RIG和疫苗接种者。法匹拉韦与狂犬病疫苗联合使用似乎可以预防致命性结局，甚至可以挽救已经表现出临床症状的病例。这种方法的临床试验是必要的，特别是在RIG可用性低的国家。
Rabies is a fatal zoonotic disease caused by the rabies virus (RABV), with almost 100% mortality if proper post -exposure prophylaxis (PEP), consisting of rabies immunoglobulin (RIG) and rabies vaccine, is not applied in a timely manner. However, this is challenged by the limited availability of RIG, especially in resource-constrained countries. In this study, we assessed the scope of the antiviral drug favipiravir to treat rabies-infected mice as an alternative to RIG. Category III-like wounds were induced in RABV-challenged mice treated with favipiravir instead of RIG in the PEP regimen. The use of favipiravir followed by rabies vaccine provided complete pro-tection against rabies-related death in 100% of mice, even after RABV propagated to the central nervous system during infection. Additionally, the virus-neutralizing antibody titer in the favipiravir and vaccine group was significantly higher than that of the RIG and vaccine recipients. The use of favipiravir with rabies vaccine seemingly prevents fatal outcomes and even rescues the cases that already express clinical symptoms. A clinical trial of this approach is warranted, especially in countries with low RIG availability.